T-butyl Substituents Research Articles

Platinum(II) phosphoryl-substituted thiourea complexes with bis-phosphine ligands and some triphenylarsine and triphenylstibine analogues

Reactions between the phosphorylthiourea ligands (EtO)2PONHC(S)NHPh (L1), (EtO)2PONHC(S)NHCH(CH3)3) (L2) and (EtO)2PONHC(S)NHCH2CH3 (L3) and cis-[PtCl2(PPh3)2] gave complexes in which the ligands bind to the platinum(II) centre as dianionic ligands. For ligands L1 and L3, the ligand binds through the thiourea sulfur and the N-alkyl nitrogen atoms, giving the distal isomer. In contrast, the ligand L2, on account of the bulky t-butyl substituent on the ligand, coordinates via the sulfur and N-phosphoryl nitrogen atoms, giving the proximal isomer. The identities of the isomers were confirmed by single crystal X-ray analysis and 31P{1H} NMR spectroscopy. The latter showing that the appearance or absence of 3J(PP) couplings between the ligand and ancillary ligands provides indicative isomeric information. Further reactions between the ligand L1 and a series of bis-phosphine, triphenylarsine and triphenylstibine platinum(II) starting complexes gave the corresponding products also as the distal linkage isomer. Computational analysis reveals a possible chalcogen bond non-covalent interaction that may be responsible for the preference for the distal isomer.

Dynamics and Coordination of a P2N2 Ligand - from Twisted Conformation to Chelation.

Based on their general spacial flexibility, their Lewis and Brønsted basicity, and ability to mimic second sphere effects the 1,5-diaza-3,7-diphosphacyclooctane ligand family and their complexes have regained substantial scientific interest. It was now possible to structurally analyze a recently reported member of this family with p-tolyl and t-butyl substituents on P and N, respectively, (P2 p-tolN2 tBu). Notably, the ligand crystallizes with a 'twisted' backbone. This compound is the very first of its kind to have been unambiguously characterized with regard to its chemical and molecular structure as being in this conformation. A temperature-dependent NMR study provides insight into the molecular dynamics of two isomers in solution, which are most likely also both twisted, as judged by the observed limited reactivity. Despite the in principle unfavorable conformation of the free ligand, it was successfully chelated to tungsten and molybdenum centers in mononuclear carbonyl complexes. The ligand, a derivative thereof and four new complexes were comprehensively characterized and analyzed in comparison. This includes single crystal XRD molecular structures of P2 p-tolN2 tBu and all four complexes. P2 p-tolN2 tBu, regardless of its twisted conformation, is able to coordinate to metal centers given that enough energy (heat) for a conformational change is provided.

Effect of tert-butyl substitution on controlling the orientation of TADF emitters in guest–host systems

We compare how changes in the structure of an acceptor–donor–acceptor TADF emitter decorated with tert-butyl groups affect alignment. The “champion” material is ICzTRZ with tBu-substitution at the distal phenyl rings of the triazine acceptors.

Chalcogen bond stabilisation of platinum(II) sulfonyl-substituted thiourea complexes with ancillary phosphine ligands

A series of sulfonyl-substituted thiourea platinum(II) complexes bearing ancillary phosphine ligands were prepared by the reaction between cis-[PtCl2(PR3)2] (PR3 = triphenylphosphine, tris(2-cyanoethyl)phosphine and 1,3,5-triaza-7-phosphaadamantane) and either p-TolSO2NHC(S)NHPh or EtSO2NHC(S)NHPh, in a refluxing Et3N/methanol mixture. The mixed ligand complexes, bearing a single phosphine and pyridine, were also prepared by the reactions between cis-[PtCl2(COD)] (COD = cyclooctadiene), pyridine and p-TolSO2NHC(S)NHPh or EtSO2NHC(S)NHPh. For each complex, the thiourea ligand binds as a dianion through the S and NPh groups in the distal isomer with a remote NSO2R group. Only in the case of the reaction between the complex cis-[PtCl2(PPh3)2] and TolSO2NHC(S)NHCH(CH3)3) was the proximal isomer formed on account of the bulky t-butyl substituent on the thiourea. X-ray structures and computational analysis revealed another reason for this preferential distal isomer formation is most likely due to the presence of a stabilising chalcogen bond, which is otherwise unavailable in the proximal isomer.

A Molecular Electron Density Theory Study of the Domino Reaction of N-Phenyl Iminoboranes with Benzaldehyde Yielding Fused Bicyclic Compounds.

The reaction of N-phenyl iminoborane with benzaldehyde yielding a fused aromatic compound, recently reported by Liu et al., has been studied within the Molecular Electron Density Theory (MEDT). Formation of the fused aromatic compound is a domino process that comprises three consecutive reactions: (i) formation of a weak molecular complex between the reagents; (ii) an intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound. The two last steps correspond to a Friedel-Crafts acylation reaction, the product of the second reaction being the tetrahedral intermediate of an electrophilic aromatic substitution reaction. However, the presence of the imino group adjacent to the aromatic ring strongly stabilizes the corresponding intermediate, being the reaction product when the ortho positions are occupied by t-butyl substituents. This domino reaction shows a great similitude with the Brønsted acid catalyzed Povarov reaction. Although N-phenyl iminoborane can experience a formal [2+2] cycloaddition reaction with benzaldehyde, its higher activation Gibbs free energy compared to the intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent, 6.6 kcal·mol-1, prevents the formation of the formal [2+2] cycloadduct. The present MEDT study provides a different vision of the molecular mechanism of these reactions based on the electron density.

Impact of pendant substituents on post-polymerization functionalization and electronic properties in stereoregular non-conjugated pendant electroactive polymers

Recent reports on non-conjugated pendant electroactive polymers (NCPEPs) have demonstrated the significance of altering structural variables specifically the stereoregularity, the nature of the pendant group and the length of the spacer connecting that group to the backbone for tuning of their optoelectronic properties. The only synthetic approach that allows for selectively studying the effects of tuning these variables without additional superimposed effects of varied molecular weights and tacticities is the post-polymerization functionalization methodology in which parent polymers are synthesized first and then functionalized with the respective pendant groups and spacers. However, specifically for tuning of the pendant group itself, the scope of such post-polymerization functionalization methods remains largely underexplored. Here, the compatibility of the established photochemical thiol-ene post-polymerization method with various pendant groups is investigated for functionalization of stereoregular and stereorandom poly(allyl methacrylates) made via anionic polymerization using an organolithium initiator. Carbazole and a family of four 3,6-disubstituted carbazoles with phenyl, methoxy, nitrile and t-butyl substituents were investigated as the respective pendant groups. With the phenyl, methoxy and nitrile substituted pendant groups limitations of the scope of the thiol-ene methodology due to limited solubility and vulnerability to photochemical side reactions could be demonstrated. In contrast, t-butyl substituents did not impede the post-polymerization functionalization. The corresponding functionalized NCPEPs were characterized and effects of substitution of the carbazole pendant group with t-butyl groups on the optoelectronic properties of the polymers are discussed. Overall, this work demonstrates critical limitations of the thiol-ene functionalization method as well as their origin when applied to differently substituted pendant groups.

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

Role of alkyl groups regulating recombination and mass transport at cobalt electrolyte-dye interface in dye sensitized solar cells

Cobalt-based one electron outer-sphere redox mediators are considered as promising alternatives to conventional I3−/I− redox electrolyte in dye sensitized solar cells (DSSC). So far, [Co(bpy)3]3+/2+ is one among the most extensively studied alternate cobalt electrolyte used in DSSC. The performance of these alternate cobalt redox shuttles varies extensively with respect to the organic sensitizers. Hence, cobalt redox mediators' selectivity as a function of structural variations in dyes needs to be studied to understand the intermolecular interactions and their effect on various charge transfer processes. In the present work, we systematically investigated the structure-property correlations of two cobalt redox mediators, [Co(bpy)3]3+/2+ and [Co(tbpy)3]3+/2+ with variable alkyl functionality (with and without t-butyl substituent) at the periphery with two carbazole based D-π-A sensitizers, CCN and TCCN having similar peripheral substituents and its role in regulating recombination and mass transport. Photovoltaic measurements reveal that even with mass transport limitation, bulky t-butyl groups effectively suppressed recombination between TiO2 and redox mediator, leading to a longer lifetime and higher open-circuit potential. Our results provide insight into the need for custom dye design, which extends the possibility of using non-conventional cobalt electrolytes like [Co(tbpy)3]3+/2+ offering better charge transfer properties.

Synthesis and antiviral activities of quinazolinamine–coumarin conjugates toward chikungunya and hepatitis C viruses

Development of new drugs with broad-spectrum to combat RNA viruses would be beneficial to mankind but faces a great challenge. We designed and efficiently synthesized a series of quinazolin-4-amine–SCH2–coumarin conjugated compounds. Our data of the virus-cell-based assay show five new conjugates inhibit chikungunya virus with EC50 values as potent as 1.96 μM and two conjugates inhibit hepatitis C virus with EC50 values as low as 16.6 μM. These conjugates possess a xylene substituent at the C-4 amino group of quinazoline and a t-butyl substituent at the C-6’ position of coumarin.

A predictive journey towards trans-thioamides/amides.

The cis-trans isomerization of (thio)amides was studied by DFT calculations to get the model for the higher preference for the cis conformation by guided predictive chemistry, suggesting how to select the alkyl/aryl substituents on the C/N atoms that lead to the trans isomer. Multilinear analysis, together with cross-validation analysis, helped to select the best fitting parameters to achieve the energy barriers of the cis to trans interconversion, as well as the relative stability between both isomers. Double experimental check led to the synthesis of the best trans candidate with sterically demanding t-butyl substituents, confirming the utility of predictive chemistry, bridging organic and computational chemistry.

Thermal- and photo-induced spin crossover in the 1D coordination polymer [Fe(4-tBupy)3][Au(CN)2]2 (4-tBupy = 4-tert-butylpyridine)

Reaction of the unidentate pyridine ligand containing a bulky t-butyl substituent with Fe2+ and [Au(CN)2]− affords a new type of spin crossover (SCO) coordination polymer in the 1D compound [Fe(4-tBupy)3][Au(CN)2]2⋅0.5H2O (1), which is formed by chains of Fe(II) complexes linked through bridging [Au(CN)2]− with three terminal 4-tBupy and one monodentate [Au(CN)2]− ligands completing the octahedral coordination around Fe(II). Longer reaction times led to the minor products [Fe(4-tBupy)2][Au(CN)2]2 (2), which presents a 2D structure more similar to that found in the other SCO compounds based on [Au(CN)2]−, and the 1D compound [Fe(4-tBupy)2(MeOH)][Au(CN)2]2 (3), in which one of the three terminal 4-tBupy found in 1 is replaced by a coordinating MeOH molecule. Magnetic measurements of 1 show an abrupt spin transition with the temperature with hysteresis and light-induced excited spin-state trapping effect. Structural analysis of 2 and 3 indicates that Fe(II) remains in the high-spin state in these compounds.

Amino pyridine iron(II) complexes: Characterization and catalytic application for atom transfer radical polymerization and catalytic chain transfer

The amino-pyridine ligand scaffold has achieved widespread use for base metal catalysis. Atom Transfer Radical Polymerization (ATRP) is one realm where base metals have achieved success in catalysis, in particular copper and iron. Herein, the synthesis and characterization of two amino-pyridine iron(II) complexes is described where the amino carbon substitution is the point of differentiation. We hypothesized that a sterically hindered, electron rich t-butyl substituent in this position might improve the propensity of said complex to achieve ATRP since inductive electron donation from the t-butyl group may improve catalyst activity and shift the ATRP equilibrium towards the active polymer species and corresponding Fe(III) complex. Dimeric 1 and 2 ([2-[(2,6-Me2-C6H3)NHCH(R)]C5H4N]FeCl2)2 (R = t-butyl or ethyl, respectively) were identified by single crystal X-ray diffraction. Both complexes favor a high-spin iron(II) state, as evidenced by Evans NMR magnetic susceptibility measurements and suggested by gas-phase computations at the M06-L level of theory. Complexes 1 and 2 catalyze styrene polymerization at elevated temperatures (120 °C) and polymerization data suggests that ATRP operates and catalytic chain transfer (CCT) competes at extended reaction times. Complex 1 with its t-butyl substituted amino carbon displays a slightly higher ATRP activity as compared to 2 [kobs(1) = 0.31 h−1; kobs(2) = 0.10 h−1], suggesting the importance of ligand optimization for future iron ATRP catalyst development.

Comparative studies of new pyranylidene-based sensitizers bearing single or double anchoring groups for dye-sensitized solar cells

Mono- and di-anchoring γ-pyranylidene-based organic dyes featuring D–π–A and D–(π–A)2 architectures have been engineered as sensitizers for applications in Dye-Sensitized Solar Cells (DSSCs). Their photophysical, electrochemical and photovoltaic properties were further investigated. TD-DFT calculations were performed to rationalize the trends observed in the optical and electrochemical properties of the dyes. The investigation of the photovoltaic performances of this series of new dyes provided structure–property relationships where their Power Conversion Efficiencies (PCE) could be correlated to structural features, such as the length of the π-conjugated spacer, the nature of the substituents on the pyranylidene electron donor moiety and the number of anchoring groups. Dye-Sensitized Solar Cells based on mono-anchoring dyes were more efficient than the corresponding cells based on di-anchoring analogues due to high dye loading. The highest Power Conversion Efficiency of 5.23% was achieved with the mono-anchoring 17a dye containing t-butyl substituent groups on the pyranylidene fragment and with one thienyl π-conjugated spacer.

Bi-functional effects of lengthening aliphatic chain of phthalimide-based negative redox couple and its non-aqueous flow battery performance at stack cell

Effects of lengthening an aliphatic chain of a phthalimide-based negative redox couple for non-aqueous flow batteries are examined. The working voltage and solubility of N-butylphthalimide are 0.1 V lower and four times greater (2.0 M) than those of methyl-substituted phthalimide. These enhanced properties are attributed to a lower packing density. Consequently, the energy density of the proposed redox couple is greatly enhanced from butyl substitution. Furthermore, the results of the stack flow cell test with N,N,N′,N′-tetramethyl-p-phenylenediamine positive redox couple show advantageous features of this non-aqueous flow battery system: a stable Coulombic efficiency and high working voltage.

Propene Polymerization with C1-Symmetric Fluorenyl-Metallocene Catalysts

Propene homopolymers have been produced by employing three C1-symmetric metallocene molecules (1, 2 and 3), each having t-butyl substituent(s) on the Cp, on the fluorenyl or on both aromatic moieties activated with methylaluminoxane at different polymerization temperatures and monomer concentrations. Polymers’ microstructures determined by 13C NMR spectroscopy suggest that the otherwise dominant alternating mechanism governed by the chain migratory insertion is largely replaced by the competing site epimerization mechanism, as a direct result of the imposing steric bulk of the t-butyl substituent on one of the distal positions of the Cp moiety. This phenomenon is more pronounced with 3 when a second t-butyl is present in the same half-space of the molecule making the site epimerization mandatory. The lower activity of catalyst 3 with respect to catalyst 2 is also in line with the necessity for the polymer chain to back-skip (or the site to epimerize) to its original position before the subsequent monomer insertion. Chain end group analyses by 1H NMR spectroscopy have revealed that the formation of vinylidene end groups, either via β-H elimination or as a result of direct chain transfer to the monomer after an ordinary 1,2-insertion is the prevailing chain termination route. A correlation between the relative concentrations of vinylidene end groups of polypropene (PP) polymers produced with each catalyst and the corresponding polypropenes’ molar masses was found, indicating the lower the relative concentrations of vinylidene end groups, the higher the molar masses.

Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives.

A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1–24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100%) against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II). The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

Pentapeptides for the treatment of small cell lung cancer: Optimisation by Nind-alkyl modification of the tryptophan side chain

The pentapeptide, tert-Prenyl4th-NH2 (DMePhe-DTrp-Phe-DTrp(N-tert-prenyl)-Leu-NH2), has recently been reported by our group to exhibit properties of substance P (SP) antagonist G against small cell lung cancer (SCLC). In this study, we undertook a systematic structure activity investigation to optimise this lead compound to improve its in vitro anti-tumour activity and biocompatibility. A series of d-tryptophan (D-Trp) derivatives were synthesised, with a range of aliphatic N-alkyl chains (methyl to pentyl) on the indole nitrogen (Nind). These were incorporated into the pentapeptide sequence by substitution of the Nind-tert-prenylated D-Trp 4th residue with the Nind-alkylated D-Trp derivatives. These pentapeptides were significantly more potent than tert-Prenyl4th-NH2, with the Nind-butyl modification generating the most cytotoxic peptides. Compared to tert-Prenyl4th-NH2, a single butyl modification on the 4th D-Trp residue (Butyl4th-NH2) showed a ∼3 fold enhancement in cytotoxicity in either the chemo-naive H69 or the DMS79 (originating from a patient treated with chemotherapeutics and radiation therapy) SCLC cell lines. In addition, the di-butylated sequence on the 2nd and 4th D-Trp residues (Butyl2nd,4th-NH2) gave ∼4.5 times higher cytotoxicity against the H69 cell line and a ∼2 fold increase against the DMS79 cell line, compared to tert-Prenyl4th-NH2. The favoured position for butyl modification was the 4th D-Trp residue, as the Butyl2nd-NH2 peptide gave lower cytotoxicity on both cell lines. Butylated peptide sequences, when exposed to neat mouse plasma for 24 h at 37 °C, were found to resist degradation with >80% remaining intact compared to ∼58% for tert-Prenyl4th-NH2. The degradation pathway in plasma occurs via de-amidation of the C-terminus, confirmed by mass spectrometry and RP-HPLC analysis. The butyl modification also conferred resistance to metabolism when tested using S9 liver fraction from mouse. The optimum analogue responsive against the DMS79 cell line was the Butyl4th-NH2 pentapeptide, which revealed a concentration dependent increase in apoptosis: the level of late apoptotic cells rose from ∼36% at 2 μM to ∼96% at 6 μM, as determined by flow cytometry, compared to the unmodified peptide that showed no such effect. Concluding, the butyl substitutions offered the best perspective for high cytotoxicity, induction of apoptosis and metabolic compatibility thereby comprising an improved broad spectrum SP antagonist candidate for treatment of SCLC.

Functionalized organic frameworks explored as second order NLO agents

A new class of chiral phthalimides functionalized with aryl piperazines was designed anticipating their strong candidature for crystal engineering and technological applications. Five new phthalimides were synthesized, characterized and subjected to single crystal X-ray diffraction study that directed their non-centrosymmetric structures. Four phthalimides crystallized in P21 space group with monoclinic crystal system, however, one was found to possess P212121 space group with orthorhombic system. The supramolecular architectures of phthalimide crystals were analysed by an approach based on consideration of energy of intermolecular interaction. The molecular hyperpolarizability (β) calculation for all the listed phthalimides indicated their promising candidature for NLO materials. Further, the crystalline form of all phthalimides was evaluated for their second harmonic generation (SHG) response. A significant response of 16.4 mV was measured for phthalimide possessing t-butyl substituent at the para position of 4-benzylpiperazine. This high SHG response may be attributed to the molecular chirality and helical supramolecular frameworks stabilized by C-H ⋯O hydrogen bonds in the solid state. The current study attests chiral phthalimides possessing arylpiperazines as effective nominees to the area of crystal engineering and nonlinear optics. New chiral phthalimides possessing terminal arylpiperazines have been studied for their solid-state properties. The second order NLO response of all the listed phthalimides was substantiated with the aid of computational study and crystal engineering approach.

Theoretical investigations of the electronic structures of carbazole-based triphenylphosphine oxide derivatives, potential bipolar host materials in blue-phosphorescent devices.

Density functional theory calculations were performed to investigate the electronic structures of bipolar host materials comprising a backbone of linked acceptor moieties where each acceptor was also linked to a pendant donor moiety. The acceptor was triphenylphosphine oxide with two of its phenyls substituted with fluorine atoms or nitrile groups (CN). The donor was carbazole (CZ) substituted, or not, with t-butyl groups. The HOMO and LUMO energy levels of these host molecules were mainly influenced by their respective hole- and electron-transport units. The t-butyl substituents on the CZ moieties had an adverse effect on the triplet energies (E T) of the host molecules, especially for molecules where the phenyls of the backbone chain were substituted with CN groups. While introducing CN substituents onto the backbone chain decreased the energy difference between the lowest singlet and triplet excited states (ΔE ST), it also caused the energy gap between the HOMO and LUMO to narrow. Among the host molecules investigated, that in which one of the phenyls in the acceptor moiety was linked to the donor while the other two phenyls in the acceptor were substituted with CN substituents exhibited the highest E T, balanced charge transport, a low charge-injection barrier, and a small ΔE ST, and is therefore a promising candidate host material for use in blue-phosphorescent devices. Graphical Abstract Density functional theory calculations were performed to explore the electronic properties of bipolar host materials comprising a backbone of linked acceptor moieties where each acceptor was also linked to a pendant donor moiety. All of the designed molecules with high triplet energies were found to be suitable for use as host materials when matched with a blue-light guest material. The results demonstrate that the host molecule in which one of the phenyls in the triphenylphosphine oxide acceptor moiety was linked to the carbazole donor while the other two phenyls in the acceptor moiety were substituted with CN substituents yields the highest blue-phosphorescent device performance, as this host molecule has interesting features such as a high E T, balanced charge transport, a low charge-injection barrier, and a small ΔE ST.

Cyclic adenosine 5'-diphosphate ribose analogs without a "southern" ribose inhibit ADP-ribosyl cyclase-hydrolase CD38.

Cyclic adenosine 5′-diphosphate ribose (cADPR) analogs based on the cyclic inosine 5′-diphosphate ribose (cIDPR) template were synthesized by recently developed stereo- and regioselective N1-ribosylation. Replacing the base N9-ribose with a butyl chain generates inhibitors of cADPR hydrolysis by the human ADP-ribosyl cyclase CD38 catalytic domain (shCD38), illustrating the nonessential nature of the “southern” ribose for binding. Butyl substitution generally improves potency relative to the parent cIDPRs, and 8-amino-N9-butyl-cIDPR is comparable to the best noncovalent CD38 inhibitors to date (IC50 = 3.3 μM). Crystallographic analysis of the shCD38:8-amino-N9-butyl-cIDPR complex to a 2.05 Å resolution unexpectedly reveals an N1-hydrolyzed ligand in the active site, suggesting that it is the N6-imino form of cADPR that is hydrolyzed by CD38. While HPLC studies confirm ligand cleavage at very high protein concentrations, they indicate that hydrolysis does not occur under physiological concentrations. Taken together, these analogs confirm that the “northern” ribose is critical for CD38 activity and inhibition, provide new insight into the mechanism of cADPR hydrolysis by CD38, and may aid future inhibitor design.